Signs of Secondary-Progressive Multiple Sclerosis

When You Stop Having Relapses, But Your MS Worsens

woman sitting on porch
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An estimated 85 percent of people with multiple sclerosis (MS) are initially diagnosed with relapsing-remitting MS (RRMS). Most of these people will eventually develop secondary-progressive MS (SPMS), which is characterized by a more steady progression of symptoms and disability and fewer or no relapses.

Before disease-modifying treatments became widely available, about 90 percent of people with RRMS eventually developed SPMS within 25 years, and about half within 10 years.

It's now unclear what effect disease-modifying therapies have on MS progression, but it's assumed (and hoped) that this proportion is lower, and SPMS is slower to develop.

Who Is More Likely to Move From RRMS to SPMS?

People can change from having RRMS to SPMS at any time, and the process may be gradual or sudden, it's variable. Generally speaking though, this transition usually occurs within 5 to 20 years after the onset of disease.

In terms of factors that may influence the transition from relapsing-remitting MS to secondary-progressive MS, studies (in untreated MS patients) show that men appear to develop SPMS quicker and at a younger age than women. In addition, those who have motor symptoms at the beginning of their MS, like difficulty walking, develop SPMS more rapidly.

What Are Some Signs that RRMS Has Become or Is Becoming SPMS?

Your medications don't work well: Despite your best efforts and adherence, some people with RRMS  on current disease-modifying drugs begin to show increasing disability and lesion burden on their MRI scans.

This could be an indication that they are no longer responding to the drugs and moving into the progressive phase of MS, or SPMS.

On the other hand, your medication not working may be due to another reason. For instance, if neutralizing antibodies to one of the interferon-based drugs are present, your neurologist may switch you to Copaxone.

Relapses are changing: The natural history of RRMS is to have the number of relapses actually decrease over time. However the relapses that do occur may be more severe, bringing multiple symptoms, rather than just affecting one area of function. In addition, recovery from the relapses tends to be incomplete, meaning that even after the acute phase of the relapse is past, some symptoms and/or disability remains. Additionally, the person no longer responds as well (or at all) to Solu-Medrol during these relapses.

Greater degree of disability: When measured by the Expanded Disability Status Scale (EDSS), people with RRMS tend to have a score of four or less. People with SPMS, on the other hand, usually have a score of six or higher -- meaning that some form of assistance is needed to walk. People with RRMS who reach a level of 4 to 5.5 (indicated by the inability to walk more than 500 meters without resting) usually develop SPMS within a fairly short time period.

There will also be more abnormalities found during the neurological exam.

This shows that the brain can no longer compensate for the demyelination from the MS.

Lastly, people that develop SPMS tend to exhibit more cognitive disturbances. This is most likely due to the greater degree of atrophy in the brain, which is highly correlated to cognitive dysfunction. What this really means is that the brain can no longer compensate for the damage, especially where there is complete axonal (nerve fiber) destruction, resulting in black holes.

Large amount of damage seen on MRI:

  • Greater lesion burden: This means that there is a greater total number of lesions, which tend to be:
  • More axonal damage and “black holes:" Areas that show up as dark (hypointense) spots on a T1 scan are referred to as “black holes.” These are areas where there has been repeated inflammation, leading to complete destruction of both myelin and the axons themselves. These areas strongly correspond to disability.
  • Enlargement of CSF-filled ventricles in the brain: This is a measure of atrophy, as there is less brain tissue, so the spaces around and within the brain get bigger.
  • Decrease in gadolinium-enhancing lesions: Paradoxically, the number of new, active gadolinium-enhancing lesions decreases in later stages of RRMS. This is because the disease is most likely becoming more degenerative than inflammatory, which is seen by more axonal damage, including atrophy and black holes.

The Bottom Line

While your disease-modifying therapies can help slow the transition from relapsing-remitting MS to secondary-progressive MS, this process inevitably happens in the majority of people. So don't place yourself at fault if you have moved from the relapsing phase of MS to the progressive phase—it's a natural process, unique for every individual, and not due to something you did.


Coyle, Patricia K. and Halper, June. Living with Progressive Multiple Sclerosis: Overcoming the Challenges (2nd Ed.) New York: Demos Medical Publishing. 2008.

Koch M, Kingwell E, Rieckmann P, Tremlett H, UBC MS Clinic Neurologists.  The natural history of secondary progressive multiple sclerosis. Journal of Neurology, Neurosurgery, & Psychiatry, 2010;81(9):1039-43.

National MS Society. Secondary Progressive MS.

Tremlett H, Yinshan Zhao, Devonshire V. Natural history of secondary-progressive multiple sclerosis. Multiple Sclerosis, 2008;14(3):314-24.

Edited by Dr. Colleen Doherty May 2nd 2016.

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